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The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis
BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is life-threatening. Several serum biomarkers, such as Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), are clinically used for evaluating AE-IPF, but these biomarkers are not adequate for establishing an early an...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936055/ https://www.ncbi.nlm.nih.gov/pubmed/31888585 http://dx.doi.org/10.1186/s12890-019-1032-2 |
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author | Hanaka, Tetsuya Kido, Takashi Noguchi, Shingo Yamada, Sohsuke Noguchi, Hirotsugu Guo, Xin Nawata, Aya Wang, Ke-Yong Oda, Keishi Takaki, Tsutomu Izumi, Hiroto Ishimoto, Hiroshi Yatera, Kazuhiro Mukae, Hiroshi |
author_facet | Hanaka, Tetsuya Kido, Takashi Noguchi, Shingo Yamada, Sohsuke Noguchi, Hirotsugu Guo, Xin Nawata, Aya Wang, Ke-Yong Oda, Keishi Takaki, Tsutomu Izumi, Hiroto Ishimoto, Hiroshi Yatera, Kazuhiro Mukae, Hiroshi |
author_sort | Hanaka, Tetsuya |
collection | PubMed |
description | BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is life-threatening. Several serum biomarkers, such as Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), are clinically used for evaluating AE-IPF, but these biomarkers are not adequate for establishing an early and accurate diagnosis of AE-IPF. Recently, the protective roles of the members of the peroxiredoxin (PRDX) family have been reported in IPF; however, the role of PRDX4 in AE-IPF is unclear. METHODS: Serum levels of PRDX4 protein, KL-6, SP-D and lactate dehydrogenase (LDH) in 51 patients with stable IPF (S-IPF), 38 patients with AE-IPF and 15 healthy volunteers were retrospectively assessed using enzyme-linked immunosorbent assay. Moreover, as an animal model of pulmonary fibrosis, wild-type (WT) and PRDX4-transgenic (Tg) mice were intratracheally administered with bleomycin (BLM, 2 mg/kg), and fibrotic and inflammatory changes in lungs were evaluated 3 weeks after the intratracheal administration. RESULTS: Serum levels of PRDX4 protein, KL-6, SP-D and LDH in patients with S-IPF and AE-IPF were significantly higher than those in healthy volunteers, and those in AE-IPF patients were the highest among the three groups. Using receiver operating characteristic curves, area under the curve values of serum PRDX4 protein, KL-6, SP-D, and LDH for detecting AE-IPF were 0.873, 0.698, 0.675, and 0.906, respectively. BLM-treated Tg mice demonstrated aggravated histopathological findings and poor prognosis compared with BLM-treated WT mice. Moreover, PRDX4 expression was observed in alveolar macrophages and lung epithelial cells of BLM-treated Tg mice. CONCLUSIONS: PRDX4 is associated with the aggravation of inflammatory changes and fibrosis in the pathogenesis of IPF, and serum PRDX4 may be useful in clinical practice of IPF patients. |
format | Online Article Text |
id | pubmed-6936055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69360552019-12-31 The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis Hanaka, Tetsuya Kido, Takashi Noguchi, Shingo Yamada, Sohsuke Noguchi, Hirotsugu Guo, Xin Nawata, Aya Wang, Ke-Yong Oda, Keishi Takaki, Tsutomu Izumi, Hiroto Ishimoto, Hiroshi Yatera, Kazuhiro Mukae, Hiroshi BMC Pulm Med Research Article BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is life-threatening. Several serum biomarkers, such as Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), are clinically used for evaluating AE-IPF, but these biomarkers are not adequate for establishing an early and accurate diagnosis of AE-IPF. Recently, the protective roles of the members of the peroxiredoxin (PRDX) family have been reported in IPF; however, the role of PRDX4 in AE-IPF is unclear. METHODS: Serum levels of PRDX4 protein, KL-6, SP-D and lactate dehydrogenase (LDH) in 51 patients with stable IPF (S-IPF), 38 patients with AE-IPF and 15 healthy volunteers were retrospectively assessed using enzyme-linked immunosorbent assay. Moreover, as an animal model of pulmonary fibrosis, wild-type (WT) and PRDX4-transgenic (Tg) mice were intratracheally administered with bleomycin (BLM, 2 mg/kg), and fibrotic and inflammatory changes in lungs were evaluated 3 weeks after the intratracheal administration. RESULTS: Serum levels of PRDX4 protein, KL-6, SP-D and LDH in patients with S-IPF and AE-IPF were significantly higher than those in healthy volunteers, and those in AE-IPF patients were the highest among the three groups. Using receiver operating characteristic curves, area under the curve values of serum PRDX4 protein, KL-6, SP-D, and LDH for detecting AE-IPF were 0.873, 0.698, 0.675, and 0.906, respectively. BLM-treated Tg mice demonstrated aggravated histopathological findings and poor prognosis compared with BLM-treated WT mice. Moreover, PRDX4 expression was observed in alveolar macrophages and lung epithelial cells of BLM-treated Tg mice. CONCLUSIONS: PRDX4 is associated with the aggravation of inflammatory changes and fibrosis in the pathogenesis of IPF, and serum PRDX4 may be useful in clinical practice of IPF patients. BioMed Central 2019-12-30 /pmc/articles/PMC6936055/ /pubmed/31888585 http://dx.doi.org/10.1186/s12890-019-1032-2 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Hanaka, Tetsuya Kido, Takashi Noguchi, Shingo Yamada, Sohsuke Noguchi, Hirotsugu Guo, Xin Nawata, Aya Wang, Ke-Yong Oda, Keishi Takaki, Tsutomu Izumi, Hiroto Ishimoto, Hiroshi Yatera, Kazuhiro Mukae, Hiroshi The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis |
title | The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis |
title_full | The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis |
title_fullStr | The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis |
title_full_unstemmed | The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis |
title_short | The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis |
title_sort | overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936055/ https://www.ncbi.nlm.nih.gov/pubmed/31888585 http://dx.doi.org/10.1186/s12890-019-1032-2 |
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